Amisulpride monotherapy may be a choice of maintenance treatment for patients with both bipolar I disorder and metabolic syndrome

To the Editor

Amisulpride is a second-generation antipsychotic (SGA) that is widely used to treat psychotic disorders with good response and few metabolic effects (Curran and Perry, 2001). However, few studies have reported the use of amisulpride to treat bipolar disorder. The present case demonstrated that moderate dosage amisulpride as monotherapy helped in the maintenance phase of bipolar disorder with metabolic syndrome.

A 23-year-old man experienced his first manic episode with psychotic symptoms when he was 20 years old (height, 165 cm; weight, 65 kg; body mass index [BMI]: 23.9; Young Mania Rating Scales [YMRS]: 46). The patient had poor drug compliance with recurrent manic episodes, and his medication was switched to olanzapine 10 mg/day monotherapy. Nevertheless, undesirable metabolic impact emerged during 6 months treatment, with body weight gain of 29 kg, to a total of 94 kg, and the development of type 2 diabetes mellitus (YMRS: 3–5; BMI: 34.5; HbA_lc: 9.3%). Because of these intolerable side effects, we substituted amisulpride 400 mg/day to treat his bipolar symptoms. Notably, the patient has maintained remission status under monotherapy with amisulpride 400 mg/day for the subsequent 2 years until now (YMRS: 3). His weight dropped to 84 kg, and he has experienced less hyperglycemia.

This case illustrates that maintenance therapy for bipolar disorder is challenging in clinical practice. SGAs (e.g. olanzapine, aripiprazole and quetiapine) are used as monotherapy for maintenance of bipolar disorder (Grunze et al., 2013), but the exact mechanism of action remains controversial and few studies have long-term clinical data.

Amisulpride at moderate to high dosage (exceeding 400 mg) decreases dopaminergic transmission through preferentially antagonizing postsynaptic D2/D3 receptors (Curran and Perry, 2001). One study showed that amisulpride at an average dosage of 786 mg/day significantly improved acute manic symptoms of subjects following 6-week treatment (Vieta et al., 2005). Our case suggests some benefits for maintenance treatment of bipolar disorder. Given the highly selective D2 and D3 actions of amisulpride, we hypothesize that dopaminergic antagonism is an important mechanism for bipolar disorder maintenance.

Additionally, amisulpride has less risk of sedation, weight gain and diabetogenic effects than other SGAs (Curran and Perry, 2001). Thus, it can help to enhance patient drug compliance and enable maintenance treatment.

To our knowledge, this is the first report of amisulpride as monotherapy in maintenance treatment for a patient with bipolar I disorder and metabolic syndrome.